Hemizygous microdeletion at 22q11.2 (22q11DS) is the most common microdeletion syndrome, usually involving homologous recombination of the same ∼3 Mb region duplicated in our patient [13]. Within the 22q11.2 duplication region, candidate genes implicated in central nervous system structure or function include CLTCL1, RTN4R, SNAP29, PRODH, GSCL, UFDIL, ES2, and COMT. The COMT gene (MIM no. 116790) has particular interest because of its role in monoamine degradation and because a common 675G > A (Val158Met) substitution results in the dysregulation of the dopaminergic system. The 675A allele of the COMT haplotype codes for the 158 Met variant of this membrane-bound enzyme that is expressed at lower levels in the brain compared to the alternate 158 Val variant [14]. A recent investigation of 126 normal healthy Caucasian subjects indicated the COMT low-expression/low-activity A allele forms part of a more expansive COMT gene haplotype “G-A-A” that appears to associate with inefficient prefrontal working-memory response [15]. This same COMT haplotype (G-A-A) also appears to be more prevalent in 22q11DS patients with OCD and ADHD [16].
